Enantioselective reductions of ethyl 2-oxo-4-phenylbutyrate by Saccharomyces cerevisiae dehydrogenases

被引:46
作者
Kaluzna, I
Andrew, AA
Bonilla, M
Martzen, MR
Stewart, JD [1 ]
机构
[1] Univ Florida, Dept Chem, Gainesville, FL 32611 USA
[2] Ceptyr, Bothell, WA 98021 USA
基金
美国国家科学基金会;
关键词
glutathione; baker's yeast; angiotensin converting enzyme;
D O I
10.1016/S1381-1177(02)00006-1
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A set of fusion proteins consisting of glutathione S-transferase linked to the N-terminus of putative dehydrogenases produced by baker's yeast (Saccharomyces cerevisiae) was screened for the reduction of ethyl 2-oxo-4-phenylbutyrate in the presence of NADH and NADPH. Two dehydrogenases-Ypr1p and Gre2p-rapidly reduced this alpha-ketoester, providing the (R)and (S)-alcohol, respectively, with high stereoselectivities. The same enzymes were over-expressed in their native forms in Escherichia coli and growing cells of the engineered strains could also be used to carry out the reductions without the need for exogenous cofactor. These results demonstrate the power of genomic fusion protein libraries to identify appropriate biocatalysts rapidly and expedite process development. (C) 2002 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:101 / 105
页数:5
相关论文
共 48 条
[1]   APPLICATION OF A PRACTICAL BIOCATALYTIC REDUCTION TO AN ENANTIOSELECTIVE SYNTHESIS OF THE 5H-2,3-BENZODIAZEPINE LY300164 [J].
ANDERSON, BA ;
HANSEN, MM ;
HARKNESS, AR ;
HENRY, CL ;
VICENZI, JT ;
ZMIJEWSKI, MJ .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1995, 117 (49) :12358-12359
[2]   A NOVEL HIGHLY DIASTEREOSELECTIVE SYNTHESIS OF CYANO ETHERS BY REGIOSELECTIVE RING-OPENING OF CHIRAL OXAZOLIDINIUM METHIODIDES WITH SODIUM-CYANIDE [J].
ANDRES, C ;
DELGADO, M ;
PEDROSA, R ;
RODRIGUEZ, R .
TETRAHEDRON LETTERS, 1993, 34 (51) :8325-8328
[3]   Stereoselective cyanation of chiral α-amino aldehydes by reaction with Nagata's reagent:: a route to enantiopure β-amino-α-hydroxy acids [J].
Andrés, JM ;
Martínez, MA ;
Pedrosa, R ;
Pérez-Encabo, A .
TETRAHEDRON-ASYMMETRY, 2001, 12 (02) :347-353
[4]   PEN-G ACYLASE CATALYZED RESOLUTION OF PHENYLACETATE ESTERS OF SECONDARY ALCOHOLS [J].
BALDARO, E ;
DARRIGO, P ;
PEDROCCHIFANTONI, G ;
ROSELL, CM ;
SERVI, S ;
TAGLIANI, A ;
TERRENI, M .
TETRAHEDRON-ASYMMETRY, 1993, 4 (05) :1031-1034
[5]   CYCLODEXTRIN-AIDED BIOCONVERSIONS AND FERMENTATIONS [J].
BAR, R .
TRENDS IN BIOTECHNOLOGY, 1989, 7 (01) :2-4
[6]   Asymmetric reduction of 2-Oxo-4-phenylbutanoic acid ethyl ester by Daucus carota cell cultures [J].
Chadha, A ;
Manohar, M ;
Soundararajan, T ;
Lokeswari, TS .
TETRAHEDRON-ASYMMETRY, 1996, 7 (06) :1571-1572
[7]   ENZYMATIC RESOLUTION OF 2-HYDROXY-4-PHENYLBUTANOIC ACID AND 2-HYDROXY-4-PHENYLBUTENOIC ACID [J].
CHADHA, A ;
MANOHAR, M .
TETRAHEDRON-ASYMMETRY, 1995, 6 (03) :651-652
[8]   A NEW PROCESS FOR THE ENANTIOSELECTIVE SYNTHESIS OF CHIRAL ALPHA-ARYLOXY AND ALPHA-HYDROXY ACIDS [J].
COREY, EJ ;
LINK, JO .
TETRAHEDRON LETTERS, 1992, 33 (24) :3431-3434
[9]   BAKERS-YEAST MEDIATED TRANSFORMATIONS IN ORGANIC-CHEMISTRY [J].
CSUK, R ;
GLANZER, BI .
CHEMICAL REVIEWS, 1991, 91 (01) :49-97
[10]   Stereochemical control in microbial reduction. 30. Reduction of alkyl 2-oxo-4-phenylbutyrate as precursors of angiotensin converting enzyme (ACE) inhibitors [J].
Dao, DH ;
Kawai, Y ;
Hida, K ;
Hornes, S ;
Nakamura, K ;
Ohno, A ;
Okamura, M ;
Akasaka, T .
BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN, 1998, 71 (02) :425-432